Structural and electrical properties of Fe-doped TiO2 thin films

The present study discusses the effect of iron doping in TiO2 thin films deposited by rf sputtering. Iron doping induces a structural transformation from anatase to rutile and electrical measurements indicate that iron acts as an acceptor impurity. Thermoelectric power measurement shows a transition between n-type and p-type electrical conduction for an iron concentration around 0.13 at.%. The highest p-type conductivity at room temperature achieved by iron doping was 10(-6) S m(-1).

Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant.

Current research and development of antigens for vaccination often center on purified recombinant proteins, viral subunits, synthetic oligopeptides or oligosaccharides, most of them suffering from being poorly immunogenic and subject to degradation. Hence, they call for efficient delivery systems and potent immunostimulants, jointly denoted as adjuvants. Particulate delivery systems like emulsions, liposomes, nanoparticles and microspheres may provide protection from degradation and facilitate the co-formulation of both the antigen and the immunostimulant. Synthetic double-stranded (ds) RNA, such as polyriboinosinic acid-polyribocytidylic acid, poly(I:C), is a mimic of viral dsRNA and, as such, a promising immunostimulant candidate for vaccines directed against intracellular pathogens. Poly(I:C) signaling is primarily dependent on Toll-like receptor 3 (TLR3), and on melanoma differentiation-associated gene-5 (MDA-5), and strongly drives cell-mediated immunity and a potent type I interferon response. However, stability and toxicity issues so far prevented the clinical application of dsRNAs as they undergo rapid enzymatic degradation and bear the potential to trigger undue immune stimulation as well as autoimmune disorders. This review addresses these concerns and suggests strategies to improve the safety and efficacy of immunostimulatory dsRNA formulations. The focus is on technological means required to lower the necessary dosage of poly(I:C), to target surface-modified microspheres passively or actively to antigen-presenting cells (APCs), to control their interaction with non-professional phagocytes and to modulate the resulting cytokine secretion profile.

Surface assembly of poly(I:C) on PEGylated microspheres to shield from adverse interactions with fibroblasts.

By expressing an array of pattern recognition receptors (PRRs), fibroblasts play an important role in stimulating and modulating the response of the innate immune system. The TLR3 ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), a mimic of viral dsRNA, is a vaccine adjuvant candidate to activate professional antigen presenting cells (APCs). However, owing to its ligation with extracellular TLR3 on fibroblasts, subcutaneously administered poly(I:C) bears danger towards autoimmunity. It is thus in the interest of its clinical safety to deliver poly(I:C) in such a way that its activation of professional APCs is as efficacious as possible, whereas its interference with non-immune cells such as fibroblasts is controlled or even avoided. Complementary to our previous work with monocyte-derived dendritic cells (MoDCs), here we sought to control the delivery of poly(I:C) surface-assembled on microspheres to human foreskin fibroblasts (HFFs). Negatively charged polystyrene (PS) microspheres were equipped with a poly(ethylene glycol) (PEG) corona through electrostatically driven coatings with a series of polycationic poly(L-lysine)-graft-poly(ethylene glycol) copolymers, PLL-g-PEG, of varying grafting ratios g from 2.2 up to 22.7. Stable surface assembly of poly(I:C) was achieved by incubation of polymer-coated microspheres with aqueous poly(I:C) solutions. Notably, recognition of both surface-assembled and free poly(I:C) by extracellular TLR3 on HFFs halted their phagocytic activity. Ligation of surface-assembled poly(I:C) with extracellular TLR3 on HFFs could be controlled by tuning the grafting ratio g and thus the chain density of the PEG corona. When assembled on PLL-5.7-PEG-coated microspheres, poly(I:C) was blocked from triggering class I MHC molecule expression on HFFs. Secretion of interleukin (IL)-6 by HFFs after exposure to surface-assembled poly(I:C) was distinctly lower as compared to free poly(I:C). Overall, surface assembly of poly(I:C) may have potential to contribute to the clinical safety of this vaccine adjuvant candidate.

Activation of electrical triggers of atrial fibrillation in hyperthyroidism.

CONTEXT: A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved. OBJECTIVE: Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease. PATIENTS AND DESIGN: Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels. MAIN OUTCOME MEASURES: The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up. RESULTS: SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability. CONCLUSION: Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.

Expression of substance P and preprotachykinin mRNA by primary sensory neurons in culture: regulation by factors present in peripheral and central target tissues.

Primary sensory neurons display various neuronal phenotypes which may be influenced by factors present in central or peripheral targets. In the case of DRG cells expressing substance P (SP), the influence of peripheral or central targets was tested on the neuronal expression of this neuropeptide. DRG cells were cultured from chick embryo at E6 or E10 (before or after establishment of functional connections with targets). Preprotachykinin mRNA was visualized in DRG cell cultures by either Northern blot or in situ hybridization using an antisense labeled riboprobe, while the neuropeptide SP was detected by immunostaining with a monoclonal antibody. In DRG cell cultures from E10, only 60% of neurons expressed SP. In contrast, DRG cell cultures performed at E6 showed a significant hybridization signal and SP-like immunoreactivity in virtually all the neurons (98%). The addition of extracts from muscle, skin, brain or spinal cord to DRG cells cultured at E6 reduced by 20% the percentage of neurons which express preprotachykinin mRNA and SP-like immunoreactivity. Our results indicate that factors issued from targets inhibit SP-expression by a subset of primary sensory neurons and act on the transcriptional control of preprotachykinin gene.

Electrical neuroimaging of memory discrimination based on single-trial multisensory learning.

Multisensory experiences influence subsequent memory performance and brain responses. Studies have thus far concentrated on semantically congruent pairings, leaving unresolved the influence of stimulus pairing and memory sub-types. Here, we paired images with unique, meaningless sounds during a continuous recognition task to determine if purely episodic, single-trial multisensory experiences can incidentally impact subsequent visual object discrimination. Psychophysics and electrical neuroimaging analyses of visual evoked potentials (VEPs) compared responses to repeated images either paired or not with a meaningless sound during initial encounters. Recognition accuracy was significantly impaired for images initially presented as multisensory pairs and could not be explained in terms of differential attention or transfer of effects from encoding to retrieval. VEP modulations occurred at 100-130ms and 270-310ms and stemmed from topographic differences indicative of network configuration changes within the brain. Distributed source estimations localized the earlier effect to regions of the right posterior temporal gyrus (STG) and the later effect to regions of the middle temporal gyrus (MTG). Responses in these regions were stronger for images previously encountered as multisensory pairs. Only the later effect correlated with performance such that greater MTG activity in response to repeated visual stimuli was linked with greater performance decrements. The present findings suggest that brain networks involved in this discrimination may critically depend on whether multisensory events facilitate or impair later visual memory performance. More generally, the data support models whereby effects of multisensory interactions persist to incidentally affect subsequent behavior as well as visual processing during its initial stages.

Correlation of Der p 2 T-cell responses with clinical characteristics of children allergic to house dust mite.

BACKGROUND: An understanding of the mechanisms responsible for the development and maintenance of allergic inflammation and their clinical implications is needed to develop specific and successful treatment for allergy. OBJECTIVES: To characterize in vitro T-cell responses to Der p 2, one of the major allergens of house dust mite (HDM), and investigate potential correlations between clinical and laboratory parameters. METHODS: Forty-two patients monosensitized to HDM and 10 age-matched, healthy children were studied. Dendritic cells pulsed with Der p 2 were used to stimulate autologous CD14(-) cells. Der p 2-specific T-cell activation markers, proliferation, and cytokine production profiles were examined. RESULTS: Der p 2-specific T-cell activation markers, proliferation, and T(H)2 cytokine production were significantly higher in HDM patients compared with healthy controls. Moreover, a significant correlation between proliferation and T(H)2 cytokine production was observed. Within the allergic group, skin reaction to HDM was significantly stronger in patients with a Der p 2-specific T-cell response. Levels of HDM-specific IgE directly correlated with interleukin 5 and interleukin 13 levels and with skin prick test results and, ultimately, with the patient's family history of allergy. Furthermore, the presence of atopic march correlated with T-cell proliferation. CONCLUSION: We found that, in HDM patients, Der p 2-specific T(H)2 responses, promoted by autologous dendritic cells in vitro, correlate with clinical parameters.

Neuronal phenotypes in mouse dorsal root ganglion cell cultures: enrichment of substance P and calbindin D-28k expressing neurons in a defined medium.

The primary sensory neurons in mouse dorsal root ganglia consist of diversified subpopulations which express distinct phenotypic characteristics such as substance P or calbindin D-28k. To determine whether neuronal phenotypes are altered or not in in vitro cultures carried out in a defined synthetic medium, dissociated dorsal root ganglion cells from newborn mice were grown in the alpha-modified minimum essential medium either supplemented with 10% fetal calf serum or serum-free. About 80% of the neurons survived after 5 days of culture in both media, but only 35% or 65% were rescued after 12 days in serum-free or fetal calf serum supplemented medium, respectively. The neuronal subpopulations expressing substance P or calbindin D-28k displayed similar morphological properties in both media and a higher resistance to culture conditions than the whole neuronal cell population, especially in serum-free medium. It is therefore concluded that a defined synthetic medium offers reproducible conditions to culture dorsal root ganglion cells for at least 5 days, stimulates the expression of substance P and enriches preferentially neuronal phenotypes expressing substance P or calbindin D-28k, for a longer period of culture.

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Spatial distribution of motor units recruited during electrical stimulation of the quadriceps muscle versus the femoral nerve.

INTRODUCTION: In this study we investigated differences in the spatial recruitment of motor units (MUs) in the quadriceps when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. METHODS: M-waves and mechanical twitches were evoked using over-the-quadriceps and femoral nerve stimulation of gradually increasing intensity from 22 young, healthy subjects. Spatial recruitment was investigated using recruitment curves of M-waves recorded from the vastus medialis (VM) and vastus lateralis (VL) and of twitches recorded from the quadriceps. RESULTS: At maximal stimulation intensity (Imax), no differences were found between nerve and over-the-quadriceps stimulation. At submaximal intensities, VL M-wave amplitude was higher for over-the-quadriceps stimulation at 40% Imax, and peak twitch force was greater for nerve stimulation at 60% and 80% Imax. CONCLUSIONS: For the VM, MU spatial recruitment during nerve and over-the-quadriceps stimulation of increasing intensity occurred in a similar manner, whereas significant differences were observed for the VL. Muscle Nerve, 2013.

Eye lens monitoring for interventional radiology personnel: dosemeters, calibration and practical aspects of H p (3) monitoring. A 2015 review.

A thorough literature review about the current situation on the implementation of eye lens monitoring has been performed in order to provide recommendations regarding dosemeter types, calibration procedures and practical aspects of eye lens monitoring for interventional radiology personnel. Most relevant data and recommendations from about 100 papers have been analysed and classified in the following topics: challenges of today in eye lens monitoring; conversion coefficients, phantoms and calibration procedures for eye lens dose evaluation; correction factors and dosemeters for eye lens dose measurements; dosemeter position and influence of protective devices. The major findings of the review can be summarised as follows: the recommended operational quantity for the eye lens monitoring is H p (3). At present, several dosemeters are available for eye lens monitoring and calibration procedures are being developed. However, in practice, very often, alternative methods are used to assess the dose to the eye lens. A summary of correction factors found in the literature for the assessment of the eye lens dose is provided. These factors can give an estimation of the eye lens dose when alternative methods, such as the use of a whole body dosemeter, are used. A wide range of values is found, thus indicating the large uncertainty associated with these simplified methods. Reduction factors from most common protective devices obtained experimentally and using Monte Carlo calculations are presented. The paper concludes that the use of a dosemeter placed at collar level outside the lead apron can provide a useful first estimate of the eye lens exposure. However, for workplaces with estimated annual equivalent dose to the eye lens close to the dose limit, specific eye lens monitoring should be performed. Finally, training of the involved medical staff on the risks of ionising radiation for the eye lens and on the correct use of protective systems is strongly recommended.